Ci a ion: Rod íguez-Fe nández, A.;
Vázquez-Cancela, O.; Piñei o-Lamas,
M.; Figuei as, A.; Zapa a-Cacha ei o,
M. Impac o he COVID-19
Pandemic on An ibio ic P esc ibing
by Den is s in Galicia, Spain: A
Quasi-Expe imen al App oach.
An ibio ics 2022,11, 1018. h ps://
doi.o g/10.3390/an ibio ics11081018
Academic Edi o s: Lo enzo Ono a o,
Ma ianna Meschia i and Timo
Juhani Lajunen
Recei ed: 2 July 2022
Accep ed: 27 July 2022
Published: 29 July 2022
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an ibio ics
A icle
Impac o he COVID-19 Pandemic on An ibio ic P esc ibing by
Den is s in Galicia, Spain: A Quasi-Expe imen al App oach
Almudena Rod íguez-Fe nández 1, Olalla Vázquez-Cancela 1,2,* , Ma ía Piñei o-Lamas 1,3 ,
Adol o Figuei as 1,3 and Ma uxa Zapa a-Cacha ei o 1,3
1Depa men o P e en i e Medicine and Public Heal h, Uni e si y o San iago de Compos ela,
15786 San iago de Compos ela, Spain; [email p o ec ed] (A.R.-F.); [email p o ec ed] (M.P.-L.);
[email p o ec ed] (A.F.); [email p o ec ed] (M.Z.-C.)
2Depa men o P e en i e Medicine, San iago de Compos ela Uni e si y Teaching Hospi al,
15706 San iago de Compos ela, Spain
3Conso ium o Biomedical Resea ch in Epidemiology & Public Heal h (CIBER en Epidemiología y Salud
Pública-CIBERESP), Uni e si y o San iago de Compos ela, 15786 San iago de Compos ela, Spain
*Co espondence: [email p o ec ed]; Tel.:+34-981950037
Abs ac :
Backg ound: An ibio ic esis ance is one o he mos p essing public heal h p oblems.
Heal h au ho i ies, pa ien s, and heal h p o essionals, including den is s, a e all in ol ed in i s
de elopmen . COVID-19 pandemic es ic ions on den al ca e may ha e had epe cussions on
an ibio ic p esc ibing by den is s. The aim o his s udy was o assess he impac o he COVID-19
pandemic on an ibio ic p esc ibing by den is s, and o e iew an ibio ic consump ion acco ding o
he WHO Access, Wa ch, Rese e classi ica ion. We conduc ed a na u al, be o e-and-a e , quasi-
expe imen al s udy, using an ibio ic p esc ip ion da a co e ing he pe iod om Janua y 2017 o May
2021. A segmen ed eg ession analysis wi h in e up ed ime se ies da a was used o analyse he
di e ences be ween he numbe s o de ined daily doses (DDD) o an ibio ics p esc ibed mon hly. The
ou comes showed an immedia e signi ican dec ease in o e all an ibio ic p esc ibing by p ima y-ca e
den is s du ing lockdown, ollowed by a non-signi ican upwa d end o he nex yea . This same
pa e n was, likewise, obse ed o Access and Wa ch an ibio ics. COVID-19 pandemic es ic ions
on den al ca e in luenced he p esc ip ion o an ibio ics. Du ing con inemen , an ini ial dec ease was
obse ed, his end changed when in pe son consul a ions we e eco e ed. I migh be bene icial o
analyse he p esc ip ion o an ibio ics using he WHO AWaRe classi ica ion, in o de o moni o hei
app op ia e use.
Keywo ds: an ibio ics; COVID-19; den is s; p esc ip ions; AWaRe classi ica ion; p ima y ca e
1. In oduc ion
An ibio ic esis ance is one o he mos p essing public heal h p oblems wo ldwide
due o i s impac on mo ali y, mo bidi y, and heal hca e cos s [
1
]. The excessi e and
inapp op ia e use o an ibio ics con ibu es a g ea deal o his p oblem. Heal h au ho i ies,
pa ien s, and heal h p o essionals a e all in ol ed in his misuse [
2
]. Den is s p esc ibe 10%
o all an ibio ics consumed [
3
,
4
] and i is es ima ed ha , om his, only 30% a e co ec ly
p esc ibed [
5
,
6
], since in den is y mos o he p ocesses can be esol ed by local ea men s,
and an ibio ics would only be indica ed on limi ed occasions [7].
The COVID-19 pandemic has had epe cussions on den al ca e, due o he isk o
c oss-con amina ion in den al clinics due o he cha ac e is ics o den al p ocedu es, du ing
which ae osols a e gene a ed, and due o he close p oximi y o he p o essional o he
pa ien [
8
]. Du ing he i s mon hs o he pandemic in Spain, medical ca e was dispensed
by means o elephone consul a ions in which he p o essional decided whe he a physical
medical isi was necessa y [
9
]. In pa ien s wi h symp oms compa ible wi h COVID-19
o suspicion o in ec ion, and wi h pain o in lamma ion o den al o igin, he isi had
An ibio ics 2022,11, 1018. h ps://doi.o g/10.3390/an ibio ics11081018 h ps://www.mdpi.com/jou nal/an ibio ics
An ibio ics 2022,11, 1018 2 o 10
o be pos poned o a minimum o wo weeks, du ing which ime den al p o essionals
had o eso o pha macological ea men wi h an ibio ics and/o analgesics [
10
]. This
elephone-based ca e, coupled wi h he ini ial di icul y o ob aining pe sonal p o ec i e
equipmen , and he ea el by p o essionals and pa ien s alike o con ac ing he disease
du ing ea men , may well ha e se ed o inc ease he numbe o an ibio ic p esc ip ions
issued wi hou an accu a e diagnosis o in ec ion, since i is ex emely complica ed o make
a di e en ial diagnosis based exclusi ely on in o ma ion p o ided by he pa ien [
9
,
11
–
13
].
Cu en ly, he impac o he COVID-19 pandemic on he sho - e m p esc ibing o
an ibio ics is unknown. Hence, he p incipal aim o his s udy was o assess he impac
o he pandemic on an ibio ic p esc ibing by den is s whose p ac ices come wi hin he
Spanish Na ional Heal h Sys em (NHS) in no h-wes Spain; he seconda y aim was o y
o assess he impac o COVID-19 on he p esc ibing o hose an ibio ic g oups ha a e
mos closely ela ed wi h he de elopmen o an ibio ic esis ance.
2. Resul s
2.1. An ibio ic P esc ibing by he WHO AWaRe Classi ica ion
P ima y-ca e den is s p esc ibed a mean o 35344 DDD o an ibio ics be o e con ine-
men , app oxima ely 6% o which belonged o he Wa ch g oup, as shown in Table 1. No
an ibio ic was p esc ibed in he Rese e g oup. The mean DDD alues o Access and Wa ch
g oup an ibio ics we e simila be o e, du ing, and a e con inemen . Amoxicillin, amoxi-
cillin combined wi h cla ulanic acid, azi h omycin, and clindamycin we e he an ibio ics
mos used by den is s. Azi h omycin, belonging o he Wa ch g oup, was he hi d mos
p esc ibed an ibio ic (Table S1).
Table 1. An ibio ic consump ion be o e, du ing and a e lockdown [14].
P e-Lockdown Lockdown Pos -Lockdown
(DDD) (DDD) (DDD)
To al An ibio ics
Mean (SD) 3,5344.73 (3606.63) 3,1767.37 (3406.07) 3,3517.72 (2329.37)
Median 35,856.17 32,554.32 34,190.74
PCT25, PCT75 3,2734.07, 3,8218.76 2,8342.59, 3,4405.20 3,2584.43, 3,5381.73
Access An ibio ics
Mean (SD) 3,3170.23 (3360.40) 3,0147.09 (3243.56) 3,1839.90 (2181.16)
Median 33,900.87 30,869.28 32,398.21
PCT25, PCT75 3,0569.86, 3,5783.69 2,6866.07, 3,2705.93 3,0942.64, 3,3819.73
Wa ch An ibio ics
Mean (SD) 2116.26 (309.18) 1555.75 (182.75) 1600.35 (195.29)
Median 2094.33 1594.00 1609.00
PCT25, PCT75 1936.13, 2340.00 1368.13, 1705.13 1483.00, 1739.17
SD: s anda d de ia ion; PCT25: pe cen ile 25; PCT75: pe cen ile 75; DDD: de ined daily dose.
2.2. Impac o he COVID-19 Pandemic on An ibio ic P esc ibing
The mon hly an ibio ic p esc ibing end om Janua y 2017 o May 2021 o p ima y-
ca e den is s is shown in Figu e 1and Table 2. As can be seen, a e seasonal adjus men ,
he e we e changes in he an ibio ic p esc ibing end p io o he ou b eak o he pandemic
(B =
−
42.39). On he eme gence o COVID-19, a signi ican dec ease in an ibio ic p esc ibing
(B =
−
3572.73; p< 0.005) was obse ed du ing lockdown (equi alen o a dec ease o
8.92% (95% CI:
−
3.80%; 14.13%)), ollowed by an immedia e non-signi ican dec ease
(B =
−
1363.82) wi h espec o he p e-pandemic pe iod, and a subsequen upwa d end in
he long e m (B = 142.74).
An ibio ics 2022,11, 1018 3 o 10
An ibio ics 2022, 11, x FOR PEER REVIEW 3 o 10
Figu e 1. Mon hly an ibio ic p esc ibing end in de ined daily doses (DDD). Blue line (−): end,
a e model adjus men ; blue dashed line: expec ed end wi h no COVID-19 ou b eak; + : mon hly
an ibio ic p esc ibing in DDD.
Table 2. Segmen ed eg ession analysis o in e up ed ime se ies da a on an ibio ic p esc ibing.[14]
An ibio ic P esc ibing (DDD)
O e all
Access
Wa ch
Pe Mon h T end in P e-Lockdown Pe iod
B
−42.39
−35.09
−7.41
95%CI
−96.47; 11.69
−87.35; 17.16
−13.52; −1.30
p- alue
0.1214
0.183
0.0187
E ec o Lockdown (1)
B
−3572.73
−2976.5
−651.02
95%CI
−6018.90; −1126.57
−5304.34; −648.65
−891.02; −411.01
p- alue
0.0051
0.0133
< 0.0001
Pos -Lockdown Change (1)
B
−1363.82
−991.28
−688.91
95%CI
−4001.04; 1273.40
−3537.90; 1555.34
−1029.54; −348.28
p- alue
0.3033
0.4373
0.0002
Change Pe Mon h in T end in Pos -Lockdown Pe iod (2)
B
142.74
136.05
29.15
95%CI
−193.39; 478.86
−190.25; 462.35
−2.28; 60.58
p- alue
0.3971
0.4057
0.0682
DDD: de ined daily dose; B: non-s anda dized coe icien ; CI: con idence in e al. 1. Wi h espec o
a p e-lockdown pe iod. 2. Wi h espec o a p e-lockdown end.
2.3. Impac o he COVID-19 Pandemic on he WHO Access G oup
Figu e 2 depic s he mon hly p esc ibing end in DDD among p ima y-ca e den is s
o he g oup o an ibio ics lis ed as Access by he WHO. Table 2 shows a s a is ically
signi ican educ ion (B = −2976.50, p = 0.0133) in an ibio ic p esc ibing du ing lockdown
(8.00% (95% CI: 2.68%; 13.46%) dec ease) ollowed by an immedia e non-signi ican e-
duc ion in p esc ibing (B = −991.28) and a non-signi ican upwa d end in he long e m
(B = 136.05).
Figu e 1.
Mon hly an ibio ic p esc ibing end in de ined daily doses (DDD). Blue line (
−
): end,
a e model adjus men ; blue dashed line: expec ed end wi h no COVID-19 ou b eak; +: mon hly
an ibio ic p esc ibing in DDD.
Table 2.
Segmen ed eg ession analysis o in e up ed ime se ies da a on an ibio ic p esc ibing [
14
].
An ibio ic P esc ibing (DDD)
O e all Access Wa ch
Pe Mon h T end in P e-Lockdown Pe iod
B−42.39 −35.09 −7.41
95%CI −96.47; 11.69 −87.35; 17.16 −13.52; −1.30
p- alue 0.1214 0.183 0.0187
E ec o Lockdown (1)
B−3572.73 −2976.5 −651.02
95%CI −6018.90; −1126.57 −5304.34; −648.65 −891.02; −411.01
p- alue 0.0051 0.0133 <0.0001
Pos -Lockdown Change (1)
B−1363.82 −991.28 −688.91
95%CI −4001.04; 1273.40 −3537.90; 1555.34 −1029.54; −348.28
p- alue 0.3033 0.4373 0.0002
Change Pe Mon h in T end in Pos -Lockdown Pe iod (2)
B 142.74 136.05 29.15
95%CI −193.39; 478.86 −190.25; 462.35 −2.28; 60.58
p- alue 0.3971 0.4057 0.0682
DDD: de ined daily dose; B: non-s anda dized coe icien ; CI: con idence in e al. 1. Wi h espec o a p e-
lockdown pe iod. 2. Wi h espec o a p e-lockdown end.
2.3. Impac o he COVID-19 Pandemic on he WHO Access G oup
Figu e 2depic s he mon hly p esc ibing end in DDD among p ima y-ca e den is s
o he g oup o an ibio ics lis ed as Access by he WHO. Table 2shows a s a is ically signi -
ican educ ion (B =
−
2976.50, p= 0.0133) in an ibio ic p esc ibing du ing lockdown (8.00%
(95% CI: 2.68%; 13.46%) dec ease) ollowed by an immedia e non-signi ican educ ion in
p esc ibing (B =
−
991.28) and a non-signi ican upwa d end in he long e m (B = 136.05).
An ibio ics 2022,11, 1018 4 o 10
An ibio ics 2022, 11, x FOR PEER REVIEW 4 o 10
Figu e 2. Mon hly WHO Access an ibio ic p esc ibing end in de ined daily doses (DDD). Blue line
(−): end a e model adjus men ; blue dashed line: expec ed end wi h no COVID-19 ou b eak; + :
mon hly an ibio ic p esc ip ions in DDD.
2.4. Impac o he COVID-19 Pandemic on he WHO Wa ch G oup
Figu e 3 depic s he mon hly p esc ibing end in DDD o Wa ch an ibio ics. Du ing
lockdown, a s a is ically signi ican educ ion (B = −651.02; p < 0.0001) in an ibio ic p e-
sc ibing was obse ed (dec ease o 20.16% (95% CI: 14.05%; 26.26%)). Whe eas he eme -
gence o COVID-19 had a signi ican impac (B = −688.91) on he end, wi h a educ ion
in p esc ibing (p = 0.0002); in he long- e m, a non-signi ican inc ease was e iden (B =
29.15).
Figu e 2.
Mon hly WHO Access an ibio ic p esc ibing end in de ined daily doses (DDD). Blue line
(
−
): end a e model adjus men ; blue dashed line: expec ed end wi h no COVID-19 ou b eak; +:
mon hly an ibio ic p esc ip ions in DDD.
2.4. Impac o he COVID-19 Pandemic on he WHO Wa ch G oup
Figu e 3depic s he mon hly p esc ibing end in DDD o Wa ch an ibio ics. Du ing
lockdown, a s a is ically signi ican educ ion (B =
−
651.02; p< 0.0001) in an ibio ic p esc ib-
ing was obse ed (dec ease o 20.16% (95% CI: 14.05%; 26.26%)). Whe eas he eme gence
o COVID-19 had a signi ican impac (B =
−
688.91) on he end, wi h a educ ion in
p esc ibing (p= 0.0002); in he long- e m, a non-signi ican inc ease was e iden (B = 29.15).
An ibio ics 2022, 11, x FOR PEER REVIEW 5 o 10
Figu e 3. Mon hly WHO Wa ch an ibio ic p esc ibing end in de ined daily doses (DDD). Blue line
(−): end, a e model adjus men ; blue dashed line: expec ed end wi h no COVID-19 ou b eak; +:
mon hly an ibio ic p esc ip ions in DDD.
3. Discussion
The da a yielded by his quasi-expe imen al s udy indica e ha he COVID-19 pan-
demic had an impo an impac on an ibio ic p esc ibing by NHS den is s in no h-wes
Spain. In Ma ch 2020, coinciding wi h he Spanish Go e nmen ’s decla a ion o a s a e o
ala m and con inemen , a signi ican dec ease was obse ed in mon hly an ibio ic p e-
sc ip ions, which was main ained du ing lockdown and ollowed by an upwa d end
ac oss he ollowing yea . This pa e n was, likewise, gene ally obse ed o an ibio ics
and o hose in he Access and Wa ch g oups, wi h 8.92%, 8.00%, and 20.16% espec i ely.
The ini ial dec ease obse ed may be a consequence o he measu es adop ed du ing
he i s phase o con inemen , in which ca e was dispensed by elephone consul a ion
and, in a e cases, in pe son [9]. Hence, he suspension o non-u gen su gical ea men s
(such as ex ac ions o asymp oma ic ee h) may ha e led o a dec ease in he p esc ibing
o an ibio ics associa ed wi h hese ypes o p ocedu es, and o Wa ch- ype an ibio ics in
pa icula [15–17]. Pa ien s’ ea o isi ing den al clinics due o he isk o becoming in-
ec ed wi h COVID-19, he smalle numbe o eme gencies, and he inc ease in sel -medi-
ca ion could also accoun o his ini ial dec ease [18–20].
The sha p d op obse ed du ing con inemen is consis en wi h ha ound in Aus-
alia [21], and con a y o ha epo ed in he Uni ed Kingdom [22,23], whe e p esc ip-
ions we e obse ed o inc ease a e he onse o he pandemic. This may be due o di -
e ences in he clinical p ac ice guidelines o hese coun ies [24]: in he case o he Uni ed
Kingdom, he ac ha p ophylac ic ea men agains in ec i e endoca di is is no en is-
aged [25] indica es ha lockdown could ha e inc eased an ibio ic p esc ip ions in an a -
emp o delay den al ca e in non-u gen ea men s [26]. Howe e , in coun ies whe e
p ophylaxis wi h an ibio ics is s anda d p ac ice, he limi ing o medical isi s du ing
lockdown also limi ed he p esc ibing o an ibio ics as p ophylaxis.
The inc ease obse ed a e con inemen can be a ibu ed o he delay in ea men
a ising om con inemen (owing o he lack o in-pe son ca e and/o pa ien ea ) [27,28]
Figu e 3. Mon hly WHO Wa ch an ibio ic p esc ibing end in de ined daily doses (DDD). Blue line
(
−
): end, a e model adjus men ; blue dashed line: expec ed end wi h no COVID-19 ou b eak; +:
mon hly an ibio ic p esc ip ions in DDD.
An ibio ics 2022,11, 1018 5 o 10
3. Discussion
The da a yielded by his quasi-expe imen al s udy indica e ha he COVID-19 pan-
demic had an impo an impac on an ibio ic p esc ibing by NHS den is s in no h-wes
Spain. In Ma ch 2020, coinciding wi h he Spanish Go e nmen ’s decla a ion o a s a e o
ala m and con inemen , a signi ican dec ease was obse ed in mon hly an ibio ic p esc ip-
ions, which was main ained du ing lockdown and ollowed by an upwa d end ac oss
he ollowing yea . This pa e n was, likewise, gene ally obse ed o an ibio ics and o
hose in he Access and Wa ch g oups, wi h 8.92%, 8.00%, and 20.16% espec i ely.
The ini ial dec ease obse ed may be a consequence o he measu es adop ed du ing
he i s phase o con inemen , in which ca e was dispensed by elephone consul a ion
and, in a e cases, in pe son [
9
]. Hence, he suspension o non-u gen su gical ea men s
(such as ex ac ions o asymp oma ic ee h) may ha e led o a dec ease in he p esc ibing
o an ibio ics associa ed wi h hese ypes o p ocedu es, and o Wa ch- ype an ibio ics
in pa icula [
15
–
17
]. Pa ien s’ ea o isi ing den al clinics due o he isk o becoming
in ec ed wi h COVID-19, he smalle numbe o eme gencies, and he inc ease in sel -
medica ion could also accoun o his ini ial dec ease [18–20].
The sha p d op obse ed du ing con inemen is consis en wi h ha ound in Aus-
alia [
21
], and con a y o ha epo ed in he Uni ed Kingdom [
22
,
23
], whe e p esc ip ions
we e obse ed o inc ease a e he onse o he pandemic. This may be due o di e ences
in he clinical p ac ice guidelines o hese coun ies [
24
]: in he case o he Uni ed Kingdom,
he ac ha p ophylac ic ea men agains in ec i e endoca di is is no en isaged [
25
]
indica es ha lockdown could ha e inc eased an ibio ic p esc ip ions in an a emp o delay
den al ca e in non-u gen ea men s [
26
]. Howe e , in coun ies whe e p ophylaxis wi h
an ibio ics is s anda d p ac ice, he limi ing o medical isi s du ing lockdown also limi ed
he p esc ibing o an ibio ics as p ophylaxis.
The inc ease obse ed a e con inemen can be a ibu ed o he delay in ea men
a ising om con inemen (owing o he lack o in-pe son ca e and/o pa ien ea ) [
27
,
28
]
which, due o he inhe en p og ession o un ea ed p ocesses, led o mo e se e e clinical
p o iles [
29
]. This e ec was also obse ed in o he diseases (cance s, ca dio ascula
diseases, diabe es) [30–32].
Be o e he pandemic, a downwa d end was obse ed in an ibio ic p esc ibing by his
g oup o p o essionals, simila o ha epo ed by s udies unde aken elsewhe e [
33
] and
he end a a na ional le el in Spain [34,35].
Amoxicillin is he leading an ibio ic used by p ima y-ca e den is s, a inding in line
wi h he esul s o o he s udies [
33
,
35
–
37
]. We de ec ed ha amoxicillin wi h cla ulanic
acid is he second leading an ibio ic, anking almos as high as amoxicillin p esc ibed
alone, e en hough i is no he an ibio ic o choice in mos clinical guidelines [
38
–
40
].
Azi h omycin anks hi d in he p esc ibing o de , despi e being an an ibio ic in he Wa ch
g oup [
14
] and i s use should be limi ed, due o he g ea e isk o he appea ance o
an ibio ic esis ance. The use o an ibio ics such as clindamycin has been associa ed wi h
an inc eased isk o C di icile in ec ions. Some s udies indica e ha app oxima ely 15% o
communi y C di icile in ec ions may be caused by odon ogenic an ibio ic p esc ibing [
41
].
O he mac olides, such as azi h omycin o cla i h omycin ha e been associa ed wi h a
highe equency o ad e se eac ions [
42
]. The use o WATCH- ype an ibio ics as well
as o he an ibio ics, such as clindamycin, should be a oided because o hei impac on
an imic obial esis ance [
14
]. These indings a e especially in e es ing, in ha hey could be
he a ge o in e en ions ha aim o imp o e den al p esc ibing.
We ound no s udy ha assessed he impac o he pandemic on an ibio ic p esc ibing
by den is s acco ding o he classi ica ion p oposed by he WHO, no any s udy ha applied
his classi ica ion o analysing p esc ip ions in his ield. This p e en s us om compa ing
ou esul s o hose o p e ious s udies and would indica e ha his classi ica ion should
also be used in s udies on den is s.
An ibio ics 2022,11, 1018 6 o 10
S eng hs and Weaknesses o he S udy
The p incipal ad an age o his s udy is he me hodology used. The ITS design makes
i possible o analyse he impac o he COVID-19 pandemic on an ibio ic p esc ibing [
43
,
44
].
By way o limi a ions, he na u e o he s udy pe se should be men ioned. The model
used assumes a linea end in he ou come, and his assump ion may only hold o e sho
in e als. Fu he mo e, he in oduc ion o da a b oken down by mon h means ha nei he
indi idual changes no he impac o he pandemic on speci ic days (a he beginning
o end o lockdown) can be shown. The s udy was ca ied ou in one egion o Spain;
he e o e, his geog aphical limi a ion could comp omise he gene alizabili y. Ano he
s udy limi a ion lies in he ac ha we do no know whe he he ini ial dec ease in he
numbe o p esc ip ions migh ha e been linked o an inc ease in he DDD o an ibio ics
p esc ibed by den is s wo king in he p i a e sec o o in hospi al eme gency se ices.
Ano he s udy limi a ion is ha he DDD o an ibio ics a e no co ela ed o he numbe s o
in-pe son consul a ions and elephone consul a ions du ing he pandemic.
Las ly, i should be s essed ha he ype o da a analysed do no eco d he eason
o p esc ibing, which means ha ou design does no allow o he app op ia eness o
p esc ip ions o be assessed. Thus, he e is a need o u he s udies ha would enable
long- e m changes in end o be analysed.
The esul s o his s udy demons a e he use ulness o using he WATCH classi ica ion
o moni o app op ia e an ibio ic p esc ibing. These esul s could be dissemina ed h ough
speci ic educa ional in e en ions o den is s o aise awa eness o he p uden use o
an ibio ics.
4. Ma e ials and Me hods
4.1. Se ings
Galicia is a egion si ua ed in he no h o Spain, wi h an a ea o 29,434 km
2
and a
popula ion o 2.7 million. Heal hca e o close o 100% o he popula ion is co e ed by
he Galician Heal h Se ice (Se izo Galego de Saúde/SERGAS). Den is y o ms pa o
p ima y ca e, wi h se ices including he examina ion o he o al ca i y, ea men o acu e
p ocesses and den al eme gencies, o al su ge ies, and p e en a i e ea men s. Fo he
emaining den al p ocedu es, such as oo canal wo k o p os he ic ehabili a ion, pa ien s
ha e o use a ne wo k o p i a e clinics, which also p o ide he ange o ea men o e ed
by SERGAS den is s. This s udy was conduc ed using an ibio ic p esc ip ion da a ela ing
o he den is s, some 100 in all, who wo k a SERGAS p ima y ca e buccoden al heal h
uni s [
45
]. In Spain, medica ions a e dispensed a pha macies and, in he case o an ibio ics,
a e only a ailable on p esc ip ions issued by den is s among o he heal h p o essionals.
4.2. S udy Design and Da a Collec ion
We used a na u al, be o e-and-a e , quasi-expe imen al design, wi h mon hly da a o
he pe iod om Janua y 2017 o May 2021. This design, which enables causal e ec s o be
es ima ed a e con olling o baseline le els and ends [
46
], is sui able o assessing he
impac o he pandemic and con inemen , since hese a e ime-delimi ed in e en ions, and
he longi udinal na u e o he da a p o ide he analysis wi h a special obus ness [47,48].
The d ug class a ge ed by his pape comp ises an ibac e ials o sys emic use
(Ana omical The apeu ic Chemical code J01) [
49
], p esc ibed in ou pa ien se ings by
den is s in he public heal h sec o .
4.3. Da a Sou ce
Fo s udy pu poses, an ibio ic p esc ip ion da a we e ob ained om he SERGAS
Pha macy In o ma ion Sys em o Complex Pha macy Se ice Analyses (Sis ema Co po-
a i o de In o mación de Análisis Complejos P es ación Fa macéu ica). This shows all
medica ions dispensed by communi y pha macies in he heal h a ea, based on o icial
p esc ip ions billed o he Public Heal h Se ice. Da a om p ima y-ca e den is s we e
selec ed. The e was no change in he sys em ac oss he s udy pe iod.
An ibio ics 2022,11, 1018 7 o 10
4.4. De ini ion o Va iables
We calcula ed he numbe o mon hly de ined daily doses (DDD), de ined as he
a e age main enance dose pe day o a d ug o i s main indica ion [50].
The Wo ld Heal h O ganisa ion (WHO) sugges s he use o he Access, Wa ch, Rese e
(AWaRe) classi ica ion issued in 2019 and upda ed in 2021, o an imp o ed e alua ion and
moni o ing use o an ibio ics. This ool makes i possible o educe an ibio ic esis ance and
access o all medicines [
14
]. The Wa ch g oup includes 110 i s - o second-choice an ibio ics
ha display a highe esis ance po en ial when compa ed wi h he Access g oup, and hus
should be s ic ly moni o ed and es ic ed o he limi ed indica ions, as well as p io i ised
as majo a ge s o s ewa dship p og ams.
4.5. S a is ical Analysis
An in e up ed ime se ies (ITS) analysis model based on a segmen ed eg ession
app oach [
44
,
51
–
53
] was pu pose-designed o analyse he di e ences be ween mon hly
p esc ibed DDD o an ibio ics [
44
]. This design allows o e ec s o be es ima ed by
con olling o baseline le els and ends [
46
]. A segmen ed linea eg ession analysis
model [
47
] was designed o analyse he di e ences obse ed om Janua y 2017 o May
2021 in e ms o p esc ibed an ibio ics. The independen a iables we e de ined as: ime
( :1, 2, 3, 53); a bina y a iable (COVID) aking alues o “0” be o e June 2020, and “1” a e
July 2020, co esponding o he ime in which he e ec o he pandemic was measu ed;
a bina y a iable (lockdown) aking alues o “1” in he mon hs o lockdown (Ma ch
2020 o June 2020), and “0” in he o he mon hs; a a iable o he ime elapsed since he
i s COVID-19 case, which ook he alue o “0” be o e; and he alues o “1”, “2”, “3”,
co esponding o he mon hs om July 2020 o May 2021. To iden i y possible seasonal
changes in an ibio ic p esc ibing, he X-13ARIMA-SEATS p ocedu e was applied [
53
].
This me hod is an adap a ion o he US Census Bu eau X-13–Au o-Reg essi e In eg a ed
Mo ing A e age (ARIMA) model which p oduces a seasonally-adjus ed ime se ies. The
Cumby-Huizinga es was used o check o au oco ela ion (10 au oco ela ion lags we e
es ed). Based on he esul s o hese es s, lags o he dependen a iable we e in oduced
o co ec o au oco ela ion. The ela i e changes due o immedia e impac and hei 95%
CI we e calcula ed acco ding o he Boos ap me hods desc ibed by Zhang [
54
]. A o al o
10,000 eplica es we e simula ed.
All analyses we e pe o med using he ee R s a is ical so wa e en i onmen ( e sion
4.0.5) [
55
], excep o he Cumby–Huizinga es , which was ca ied ou wi h S a a e sion
12 [56].
5. Conclusions
The COVID-19 pandemic led o a dec ease in an ibio ic p esc ibing by p ima y-ca e
den is s du ing he ini ial mon hs, ollowed by an upwa d end. This change was like-
wise obse ed o Access and Wa ch an ibio ics. Due o he high pe cen age o an ibio ic
p esc ip ions issued by hese p o essionals, i may well be o in e es i u u e s udies ha
analysed an ibio ic p esc ibing among den is s we e o use he WHO AWaRe classi ica ion.
Supplemen a y Ma e ials:
The ollowing suppo ing in o ma ion can be downloaded a : h ps:
//www.mdpi.com/a icle/10.3390/an ibio ics11081018/s1, Table S1: De ined daily dose by ac i e
ing edien as p esc ibed by p ima y-ca e den is s, acco ding o he AWaRe Classi ica ion [49].
Au ho Con ibu ions:
Concep ualiza ion, A.F. and M.Z.-C.; Da a cu a ion, A.R.-F., O.V.-C., M.P.-L.,
A.F. and M.Z.-C.; Fo mal analysis, A.R.-F., M.P.-L., A.F. and M.Z.-C.; Funding acquisi ion, A.F. and
M.Z.-C.; In es iga ion, A.R.-F., O.V.-C., M.P.-L., A.F. and M.Z.-C.; Me hodology, O.V.-C., M.P.-L., A.F.
and M.Z.-C.; P ojec adminis a ion, A.F. and M.Z.-C.; Resou ces, A.R.-F., O.V.-C., M.P.-L., A.F. and
M.Z.-C.; So wa e, A.R.-F., O.V.-C., M.P.-L., A.F. and M.Z.-C.; Supe ision, M.P.-L., A.F. and M.Z.-C.;
Valida ion, A.R.-F., O.V.-C., M.P.-L., A.F. and M.Z.-C.; Visualiza ion, A.R.-F., O.V.-C., M.P.-L., A.F.
and M.Z.-C.; W i ing—o iginal d a , A.R.-F., O.V.-C., M.P.-L., A.F. and M.Z.-C.; W i ing— e iew &
An ibio ics 2022,11, 1018 8 o 10
edi ing, A.R.-F., O.V.-C., M.P.-L., A.F. and M.Z.-C. All au ho s ha e ead and ag eed o he published
e sion o he manusc ip .
Funding:
This s udy has been unded by he Ins i u o de Salud Ca los III (ISCIII) h ough he p ojec
PI19/01006, co- inanced by FEDER, Eu opean Union.
Ins i u ional Re iew Boa d S a emen : No applicable.
In o med Consen S a emen : No applicable.
Da a A ailabili y S a emen :
The da ase s used and/o analysed du ing he cu en s udy a e
a ailable om he co esponding au ho on easonable eques .
Acknowledgmen s:
We would like o hank he Subdi ec o a e-Gene al o Pha macology o he
Galician Regional Au ho i y (Xun a de Galicia) o u nishing he p esc ip ion da a needed o conduc
his s udy.
Con lic s o In e es : The au ho s decla e no con lic o in e es .
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